The Pediatric AIDS Clinical Trials Group (PACTG) remains the preeminent organization in the world for evaluating treatments for HIV-infected children and adolescents, and for developing new approaches for the interruption of mother-to-infant transmission. It has set the standards of care for children infected with HIV and for the interruption of vertical transmission, and for research on HIV pathogenesis in infants and children. The PACTG is a multi-center, multidisciplinary investigative group. This cooperative agreement concerns the PACTG Coordinating and Operations Center (CORC), which include support for the Group Leader, the Executive Committee, other standing committees, a Community Constituency Group, the Operations Center, and the Core Laboratories. Associated with the CORC, under separate applications, are 18 Pediatric AIDS Clinical Trials Units and a Statistical and Data Management Center. The Group will be managed by an Executive Committee, which will oversee an integrated research agenda developed by five Research Agenda Committees (Perinatal Transmission, Primary Therapy, Complications of HIV, Immunology/Immune-Based Therapy Vaccine, and Adolescent), three Scientific Committees (Virology, Immunology, and Pharmacology), and three Resource Committees (Community Constituency Group, Pediatric Site Resource Committee, and the International Committee). The scientific agenda of the PACTG encompasses the critical issues that impact mother-to-infant transmission and treatment of HIV-infected children and adolescents. The four primary goals of the PACTG's scientific agenda are (1) to optimize strategies to maintain or improve mother-to-infant transmission at <2% without long-term toxicity to exposed infants or treated pregnant women in the U.S.; (2) to enable >90% of children perinatally infected with HIV to achieve normal growth and development, and >20 years survival in the U.S. ; (3) to determine the pharmacologic, immunologic and behavioral characteristics unique to adolescents and to develop improved strategies for therapeutic intervention that will enable adherence of >75% of youth receiving antiretroviral therapy; and (4) to use both domestic and international sites, to develop simpler and more effective treatment interventions that will prolong survival of HIV-infected children while retaining optimal quality of life.